Membrane-bound transcription factor protease site 2, also known as site-2 protease, is a zinc metalloprotease in the Golgi membrane. It regulates cholesterol metabolism and unfolded protein response. When cells are deprived of cholesterol, sterol regulatory element-binding proteins move from the endoplasmic reticulum to the Golgi apparatus and are cleaved by site-1 protease and site-2 protease sequentially to release the active amino-terminal domains. These amino-terminal domains of SREBPs then translocate into the nucleus to induce expression of genes for cholesterol biosynthesis. During UPR, activating transcription factor 6 transports from ER to Golgi apparatus and is cleaved by S1P and S2P to release a cytosolic fragment. This cytosolic fragment relocates to the nucleus and activates the UPR gene expression.
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